In aging advanced countries, agnostic patients go on increasing and the increase becomes recognized as a serious problem. Agnosia is classified into cerebrovascular agnosia, caused by cerebrovascular disease, and Alzheimer's disease. Alzheimer's disease is known as a large part of the cause of developing senile agnosia and deteriorates QOL (Quality of Life) of the patients because it gives rise to memory disorder and movement disorder. Alzheimer's disease requires considerable nursing care in addition to the treatment of the disease and also raises the cost of health care and social burdens such as time loss, loss of working opportunity and psychological burden of the patients, their families and care-givers. Alzheimer's disease is one of serious neurodegenerative diseases with no fundamental treating method. The pathologic characteristics of the disease are the deposition of “senile plaque”, i.e., the accumulation of Aβ consisting of 40 (SEQ ID NO:1) or 42 (SEQ ID NO:2) amino acid residues to central nerve, the neurofibrillary degeneration and the degeneration and deficiency of nerve cells. For treating Alzheimer's disease, the treatment using cholinesterase inhibitor and clinical trials using cholesterol-lowering agent and cerebral nerve-protective agent such as ethyl-EPA are carried out.
Also, expecting the permanent cure, the development of vaccines for preventing the target molecule, Aβ which is a major cause of Alzheimer's disease, is now in progress (Rf. Agadjanyan M. G. et al., Journal of Immunology, Vol. 174, No. 3. pp. 1580-1586 (2005)). In addition, the development of human anti-Aβ monoclonal antibodies, DNA vaccines, novel adjuvants such as CpGDNA, and peptide vaccines for oral administration is also in progress. However, DNA vaccines are restricted by major histocompatibility antigen (hereinafter, abbreviated as “MHC”) class I and tend to induce the activation of cytotoxic T-cell. Peptide vaccines have low immunogenicity and require adjuvant for inducing antibodies because they defect the ability of inducing antibodies against Aβ. When the antigen has a relatively high molecular weight, the immunological reaction to the epitopes has a possibility of causing unexpected inflammatory responses because the antigen has many T-cell or B-cell epitopes. Further, the inflammatory responses give a risk of causing encephalitis as a side effect. Therefore, the fundamental treating method for Alzheimer's disease has not been established yet. Although Aβ is known to involve in the development and progression of various diseases except for Alzheimer's disease, the preventing method and treating method for those diseases have not been established yet.
To overcome those problems, the present inventors disclosed that a peptide vaccine; designed to have an amino acid sequence of cell attachment motif in a peptide which is designed to have an amino acid sequence including T-cell epitope at the amino terminus, linker peptide, and an amino acid sequence including B-cell epitope at the carboxyl terminus; can be used for inducing the production of antibodies specific to Aβ and for treating Alzheimer's disease (Ref. International Patent Application No. WO 2004/87767). However, the specific amino acid sequence of the peptide vaccine usable to overcome the problems is not described in the specification of International Patent Application No. WO 2004/87767. Further, it was revealed that the overlapping-shift-type multiagretope peptide (SEQ ID NO:3, hereinafter, abbreviated as “OMP”) and a peptide (SEQ ID NO:4, hereinafter, abbreviated as “Gag”) having an amino acid sequence of the 298th to 312nd of Gag protein originated from human immunodeficiency virus (hereinafter, abbreviated as “HIV”), described in International Patent Application No. WO 2004/87767, have low activities for inducing the production of antibodies specific to Aβ when they are used as T-cell epitopes. For inducing the production of antibodies specific to Aβ in many patients of Alzheimer's disease as possible, it is necessary to design a T-cell epitope which is restricted by many human MHC class II haplotypes, i.e., HLA (human leucocyte antigen)-DR haplotypes (allele) as possible and is able to induce the production of antibodies specific to Aβ strongly. As a peptide vaccine used for preventing and/or treating Alzheimer's disease and other various neurodegenerative diseases, it is desired that the peptide is able to inhibit the progress of symptoms rapidly, to induce the production of antibodies specific to Aβ effectively by low administration frequency as possible from the viewpoint of economical cost, and has a smaller risk to induce serious side-effects when it is administered to human.